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Similarities between Johne's disease in ruminants and Crohn's disease in humans have led to speculation that Mycobacterium avium paratuberculosis (MAP) might be a causative agent in Crohn's disease. However, evidence remains inconsistent. In this case-control study (1999-2004), the authors assessed the possible role of drinking water and dairy products potentially contaminated with MAP in the etiology of Crohn's disease. A total of 218 patients with Crohn's disease recruited from nine hospitals in England and 812 controls recruited from the community completed a short questionnaire for evaluation of proxy measures of potential exposure to MAP. Logistic regression showed no significant association with measures of potential contamination of water sources with MAP, water intake, or water treatment. Multivariate analysis showed that consumption of pasteurized milk (per kg/month: odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.69, 0.97) was associated with a reduced risk of Crohn's disease. Meat intake (per kg/month: OR = 1.40, 95% CI: 1.17, 1.67) was associated with a significantly increased risk of Crohn's disease, whereas fruit consumption (per kg/month: OR = 0.78, 95% CI: 0.67, 0.92) was associated with reduced risk. This study does not support a role for water or dairy products potentially contaminated with MAP in the etiology of Crohn's disease. The observed association with meat and the negative association with pasteurized milk need further study. [ABSTRACT FROM AUTHOR]

Background: The teaching of anatomy to medical undergraduates continues to develop. Medical imaging can accurately demonstrate anatomy. 'disect' is a computer program which manipulates and reconstructs real CT images in 3-D. Aim: To implement and assess a novel computer-based imaging resource. Methods: Third-year undergraduate medical students at the University of East Anglia were randomised to different methods of delivering the program - either self-directed use or guided use with worksheets. Knowledge of gastro-intestinal anatomy was assessed using a 20-item test. Attitudes to using 'disect' were evaluated using Likert scales. Results: Most students reported the program was easy to use and a valuable resource for learning anatomy. There was no difference in scores between guided use and self-directed use (10.7 marks versus 10.6 marks, p¼0.52). Students who undertook the anatomy special study module, which involved dissection of the digestive system, performed best (12.8 marks versus 9.9 marks, p¼0.005). Conclusion: Students can adequately use a computer program to see major anatomical structures derived from CT scans. Students reported that learning anatomy can be aided by the imaging-based resource. Learning anatomy is a multi-modal activity and packages like 'disect' can enhance learning by supplementing current teaching methods. [ABSTRACT FROM AUTHOR]

Holoprosencephaly (HPE) is one of the most common malformations in embryonic development. HPE represents a continuum spectrum that involves the midline cleavage of forebrain structures. Facial malformations of varying degrees of severity are also observed. It is probable that HPE results from a combination of genetic mutations and environmental influences during the initial weeks of pregnancy. Some patients with HPE experience early death, whereas others go on to experience neurodevelopmental impairment. Accurate fetal imaging can facilitate diagnosis and prenatal counseling, although more subtle brain abnormalities can be difficult to diagnose prenatally. Fetal counseling can be complex, given that the etiopathogenesis remains unclear and variable penetrance is prevalent in inherited genetic mutations. The aim of this narrative review is to examine the literature on HPE and to offer recommendations for pediatric neurologists for fetal counseling and postnatal care., Competing Interests: Declaration of competing interest The authors report no conflict of interest or competing financial interests in relation to the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists., Competing Interests: Declaration of competing interest The authors report no conflict of interest or competing financial interests in relation to the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine if an intervention designed to enhance early responsive parenting (RP) practices (e.g., reading infant cues, establishing bedtime routines) and promote infant sleep and soothing among Black families has secondary benefits for mothers' postpartum sleep., Method: This preregistered secondary analysis of the Sleep Strong African American Families randomized controlled trial investigated effects of an RP intervention versus a safety control condition on self-reported maternal sleep difficulties at 8 and 16 weeks postpartum and on actigraph-measured maternal sleep at 8 weeks postpartum., Results: The 212 randomized mothers were Black/African American (100%) and non-Hispanic (98.6%) and averaged 22.7 years ( SD = 4.5) of age. Among 138 mothers with useable actigraph data, RP mothers had a mean 20 [95% CI: 2, 37] minutes longer actigraph-measured total sleep time than controls at 8 weeks postpartum, after adjusting for age and other covariates likely to influence mothers' sleep ( p = .04). Participation in the RP intervention did not significantly impact self-reported sleep difficulties or other actigraph-measured sleep parameters (e.g., efficiency) in either unadjusted or adjusted models, although RP effects on sleep difficulties and sleep efficiency were in the hypothesized directions., Conclusions: Interventions supporting responsive sleep parenting practices to increase infant sleep may also help first-time Black mothers get more sleep themselves during the postpartum period, even without an explicit focus on maternal sleep strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The growing understanding of the role of extracellular vesicles (EVs) in embryo-maternal communication has sparked considerable interest in their therapeutic potential within assisted reproductive technology, particularly in enhancing implantation success. However, the major obstacle remains the large-scale production of EVs, and there is still a gap in understanding how different culture systems affect the characteristics of the EVs. In the current study, trophoblast analogue human chorionic carcinoma cell line was cultivated in both conventional monolayer culture (2D) and as spheroids in suspension culture (3D) and how the cell growth environment affects the physical, biochemical and cellular signalling properties of EVs produced by them was studied. Interestingly, the 3D system was more active in secreting EVs compared to the 2D system, while no significant differences were observed in terms of morphology, size, and classical EV protein marker expression between EVs derived from the two culture systems. There were substantial differences in the proteomic cargo profile and cellular signalling potency of EVs derived from the two culture systems. Notably, 2D EVs were more potent in inducing a cellular response in endometrial epithelial cells (EECs) compared to 3D EVs. Therefore, it is essential to recognize that the biological activity of EVs depends not only on the cell of origin but also on the cellular microenvironment of the parent cell. In conclusion, caution is warranted when selecting an EV production platform, especially for assessing the functional and therapeutic potential of EVs through in vitro studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khan, Muhandiram, Dissanayake, Godakumara, Midekessa, Andronowska, Heath, Kodithuwakku, Hart and Fazeli.)

Objective: To collect data on content/face validity and interobserver agreement for a Neonatal Coma Score (NCS) in well full-term neonates and on construct validity in unwell and preterm babies, specifically how the NCS changed with gestational age and illness., Design: Prospective cohort studies., Setting: Two UK tertiary neonatal units (Sheffield and Leeds)., Patients: 151 well full-term (≥37 weeks gestational age) newborn babies recruited between January and February 2020 in Sheffield and April and May 2021 in Leeds; 101 sick preterm and full-term babies admitted to Sheffield neonatal unit between January 2021 and May 2022., Intervention: A new NCS., Main Outcome Measures: Determination of normal values in well babies born ≥37 weeks gestational age; data on how the NCS changes with gestational age and illness., Results: Face validity was demonstrated during development of the NCS. The median NCS of well, full-term newborn babies was 15 and the intraclass correlation coefficient was 0.78 (95% CI 0.70 to 0.84). In the 'well' preterm population, 95% <28 weeks had a score ≥11; 28-31 weeks ≥11; 32-36 weeks ≥13 and 37-44 weeks 14-15. The NCS dropped during periods of deterioration, demonstrating evidence of construct validity. Criterion validity was not assessed., Conclusions: The NCS has good intraobserver agreement in well full-term babies, with a normal NCS 14-15. The NCS in preterm neonates depended on gestational age, and deterioration from baseline was associated with illness. Further work is needed to determine normal scores each gestational age, reliability at lower levels, how early the NCS identifies deterioration and comparison with other assessment tools to demonstrate criterion validity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe families' experiences of antenatal counselling of spina bifida., Design: Systematic review., Methods: MEDLINE, CINAHL, PsycINFO and Embase databases were searched using a combination of Medical Subject Headings and text/abstract terms. Case reports, survey results and qualitative interview data were included. The quality of research was evaluated using the Critical Appraisal Skills Programme checklist., Results: 8 papers were included. Families described shock and grief at diagnosis, with some immediately offered termination of pregnancy (TOP) even though they knew little about the condition. Positive and negative aspects of care were found. Teams that were gentle, kind and empathetic, who did not use jargon, and highlighted positive and negative aspects of the baby's life were seen favourably. Callous language, and overly negative or incorrect counselling was not, particularly if there was pressure to agree to TOP. Families based their decisions on how they would cope, the effect on siblings and the baby's likely quality of life. Prenatal surgery was viewed positively. The views of families who chose TOP, were happy with their care, partners, families, and the LGBTQ+ community were under-represented in the literature., Conclusions: Unlike other conditions where limited data on outcome exist or the spectrum is genuinely broad, the outcomes of children with spina bifida is well described. Poor aspects of antenatal counselling were described frequently by families, and further work is needed to capture the full spectrum of views on antenatal counselling, how it can be improved, and what training and resources healthcare professionals need to perform it better., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An 8-week educational intervention co-taught by medical students and faculty was designed to foster communication between clinical researchers and populations of interest to ultimately increase participation in clinical research by older adults, including underrepresented groups. Weekly topics focused on age-related changes and health conditions, socio-contextual factors impacting aging populations, and wellness strategies. Objectives: To evaluate the successes and weaknesses of an educational intervention aimed at increasing the participation of older adults in clinical research. Design: A focus group was assembled after an 8-week educational intervention, titled DREAMS, to obtain participants' feedback on the program, following a pre-formulated interview guide. Settings: Participants were interviewed in a health center office environment in the United States of America in April of 2016. Participants: A post-intervention focus group was conducted with a group of eight older adults (mean age = 75.8 ± 11.4 years) from 51 total participants who completed the intervention. Methods: The focus group was interviewed loosely following a pre-formed question guide. Participants were encouraged to give honest feedback. The conversation was recorded, transcribed verbatim, and analyzed using thematic analyses. Results: While participants viewed most aspects of the study as a success and stated that it was a productive learning experience, most participants had suggestions for improvements in the program content and implementation. Specifically, the composition of and direction to small breakout groups should be carefully considered and planned in this population, and attention should be paid to the delivery of sensitive topic such as death and dementia. A clear main benefit of this programmatic approach is the development of a rapport amongst participants and between participants and clinical researchers. Conclusions: The results provide useful insights regarding improving participation among hard-to-reach and historically underrepresented groups of older adults in clinical research. Future iterations of this program and similar educational interventions can use these findings to better achieve the programmatic objectives.

The flooding record of North America has been used to infer patterns of global erosion and sea level in deep time. Here, we utilize the geospatial dimension of the stratigraphic record provided by the Macrostrat database, and patterns of erosion from thermochronology, to resolve local tectonic subsidence from global sea level. We show that the flooding history of North America correlates in space and time with continent-facing subduction along active margins, consistent with subduction-driven dynamic topographic subsidence of the continental interior. Nonetheless, the continentally aggregated flooding signal of North America is an exaggerated global M-curve of Phanerozoic sea level. This coincidence relates to the closing of the geodynamic loop of the supercontinent cycle: Subduction under North America accommodated both the makeup and breakup of Pangaea, which, coupled with changing ridge length, flattened hypsometry, and increased sea level both locally and globally. The sole Phanerozoic exception to this pattern of global sea level tracking North American near-field geodynamics is the Cambrian Sauk transgression. We argue that this is a far-field record of the inception of circum-Gondwanan subduction, independent of North America, which significantly flattened Earth's hypsometry. This hypsometric flattening displaced ocean water globally, flooding tectonically passive North America to seal the Great Unconformity.

Objectives: Health education may improve health in geriatric patients. To evaluate differences between remote and in-person education, the DREAMS ( D eveloping a R esearch Participation E nhancement and A dvocacy Training Progra m for Diverse S eniors ) health seminar series compared in-person and remote learning groups to assess feasibility, satisfaction, adherence, health literacy, and cognitive outcomes., Research Design: Nonrandomized two-arm interventions occurred remotely or in-person. About 130 diverse, older adults ( M age: 70.8 ± 9.2 years; in-person n = 95; remote, n = 35) enrolled. Data from 115 completers (In-person n = 80; Remote n = 35) were analyzed for performance outcomes. Feasibility, adherence, and satisfaction benchmarks were evaluated at baseline, immediately post intervention, and 8 weeks post intervention. Adjusting for baseline performances, outcomes on health literacy and cognitive measures were compared between groups after intervention (at posttest and at 8-week follow-up) using adjusted mean differences (β coefficients)., Results: Eighty in-person and all remote participants completed at least six modules. Both programs had high satisfaction, feasibility, and strong adherence. After adjusting for demographic covariates and baseline values, cognitive and motor cognitive measures between groups were domain specific (e.g., global cognition, executive function, spatial memory, mental tracking capacity, and cognitive integration)., Discussion and Implications: This work explores feasible measures of knowledge acquisition and its link to health literacy and cognitive outcomes. Identifying effective delivery methods may increase involvement in clinical research. Future studies may encourage remote learning for increased accessibility.

Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial-derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by the menstrual cycle hormones estrogen (E2; proliferative phase), progesterone (P4; secretory phase), and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentrations and sizes of particles and EV proteomic analysis was performed using shotgun label-free mass spectrometry. Our results showed that although endometrial derived EVs were secreted in numbers independent of hormonal stimulation, EV sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EV's proteome, with proteins enhanced within the EV E2P4 group shown to be involved in different processes, such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs.

The current study examined concurrent and longitudinal associations between experiences of racial discrimination and private regard (i.e., feelings about being Black and other Black people) among 346 Black early adolescents who completed four assessments over two years. Between-person (interpersonal) and within-person (intrapersonal) effects were tested to provide a rigorous and comprehensive examination of these associations. There was minimal evidence of significant between-person effects in which youth experiencing varying levels of racial discrimination differed in their private regard. However, at the within-person level, there were significant negative concurrent associations between racial discrimination and private regard, indicating that youths' positive racial identity was undermined at times when they were encountering higher levels of racial discrimination than they typically did. Results highlight significant intrapersonal links between racial discrimination and private regard and underscore the continued need for interventions to eliminate racial discrimination and to support Black youth experiencing it.

Background: Parkinson's disease (PD) affects both men and women with documented gender differences across functional domains, with findings varying among reports. Knowledge regarding gender differences in PD for different geographic locations is important for further understanding of the disease and for developing personalized gender-specific PD assessment tools and therapies., Objective: This study aimed to examine gender differences in PD-related motor, motor-cognitive, cognitive, and psychosocial function in people with PD from the southern United States (US)., Methods: 199 (127 men and 72 women; M age: 69.08±8.94) individuals with mild-moderate idiopathic PD (Hoehn &Yahr (H&Y) Median = 2, stages I-III) from a large metro area in the southeastern US were included in this retrospective, cross-sectional study. Motor, motor-cognitive, cognitive, and psychosocial data were obtained using standardized and validated clinical tests. Univariate analyses were performed, adjusting for age and housing type., Results: After adjustment for age, housing, PD duration and fall rate, men exhibited statistically significantly greater motor (Movement Disorders Society (MDS)-Unified Parkinson Disease Rating Scale (UPDRS)-II) and non-motor (MDS-UPDRS-I) impact of PD, and more severe motor signs (MDS-UPDRS-III). Men exhibited worse PD-specific health-related quality of life related to mobility, activities of daily living, emotional well-being, cognitive impairment, communication, and more depressive symptoms. Men performed worse on a subtraction working memory task. Women had slower fast gait speed., Conclusions: In the southeastern United States, men may experience worse PD-related quality of life and more depression than women. Many non-motor and motor variables that are not PD specific show no differences between genders in this cohort. These findings can contribute to the development of gender-sensitive assessment and rehabilitation policies and protocols for people with PD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abraham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study evaluated initial information about psychosocial differences of 130 diverse, older adults ( M age: 70.8 ± 9.2 years) who received a "low-tech" remote (independent reading with telephone support) or in-person education through DREAMS ( Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors ) health seminar series. Outcomes on measures of depression, quality of life, and spatial extent of lifestyle of 115 completers were analyzed at baseline, immediately post-intervention, and 8-week follow-up. Adjusted at baseline, psychosocial outcomes were compared between groups at post-test and 8-week follow-up using adjusted mean differences. Post-participation, compared to remote participants, in-person participants had significantly lower depression on Beck Depression Inventory-II, Geriatric Depression Scale, and significantly higher mental quality of life on Short Form-12. This study links knowledge acquisition via in-person learning with decreased stress, depression, and increased quality of life among seniors. Identifying effective educational delivery methods may increase clinical research involvement for aging communities.

Experiences of racial discrimination are common among Black youth and predict worse mental health cross-sectionally and over time. Additional research is needed to address lingering questions regarding the direction of effect(s) underlying these patterns, differences in the magnitude of effects across adolescence, and gender differences. To address these gaps, the current study tested bidirectional linkages between racial discrimination and depressive symptoms at the between- (interpersonal) and within- (intrapersonal) level using 4 waves of data from 889 Black youth (54% female) from Georgia and Iowa. Participants reported experiences of racial discrimination and depressive symptoms at ages 10.6 years (Wave 1), 12.5 years (Wave 2), 15.7 years (Wave 3), and 18.8 years (Wave 4). The cross-lagged panel model (CLPM) was used to examine between-person associations over time, and the random intercept cross-lagged panel model (RI-CLPM) was used to examine within-person associations over time. Results were consistent across models, revealing significant concurrent associations between racial discrimination and depressive symptoms, significant lagged effects from racial discrimination to depressive symptoms, and no significant lagged effects from depressive symptoms to racial discrimination. Effects did not differ across adolescence, and there were few gender differences in the degree of association between racial discrimination and depressive symptoms. Findings provide rigorous evidence that experiencing greater racial discrimination is associated with increases in depressive symptoms throughout adolescence and add to a growing body of work showing that racial discrimination can undermine mental health and well-being among Black youth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Overlapping disease aetiologies associated with multiple altered biological processes have been identified that change the endometrial function leading to recurrent implantation failure (RIF) and recurrent early pregnancy loss (REPL). We aimed to provide a detailed insight into the nature of the biological malfunction and related pathways of differentially expressed genes in RIF and REPL. Endometrial biopsies were obtained from 9 women experiencing RIF, REPL and control groups. Affymetrix microarray analysis was performed to measure the gene expression level of the endometrial biopsies. Unsupervised clustering of endometrial samples shows scattered distribution of gene expression between the RIF, REPL and control groups. 2556 and 1174 genes (p value < 0.05, Fold change > 1.2) were significantly altered in the endometria of RIF and REPL patients’ group, respectively compared to the control group. Downregulation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the differentially expressed genes (DEGs) in RIF and REPL including ribosome and oxidative phosphorylation pathways. Gene Ontology (GO) analysis revealed ribosomes and mitochondria inner membrane as the most significantly downregulated cellular component (CC) affected in RIF and REPL. Determination of the dysregulated genes and related biological pathways in RIF and REPL will be key in understanding their molecular pathology and of major importance in addressing diagnosis, prognosis, and treatment issues

Background: The neurological examination of an unwell neonate can aid management, such as deciding if hypothermia treatment is warranted in hypoxic ischaemic encephalopathy or directing investigations in hypotonic neonates. Current standardised examinations are not designed for unwell or ventilated neonates, and it is unclear how confident paediatricians feel about the examination or what aspects they perform.  AIM: This study aimed to review the confidence of UK paediatricians on the neurological examination in unwell neonates, describe their attitudes towards it, and determine what could improve practice., Methods: An explanatory sequential mixed methods approach (QUAN → QUAL) with equal weighting between stages. A survey on attitudes to the neonatal neurological examination was sent to all UK neonatal units and members of the British Paediatric Neurology Association. Volunteers were sought for semi-structured interviews. Thematic analysis was used to interpret qualitative data, which was triangulated with quantitative questionnaire data., Results: One hundred ninety-three surveys were returned, 31.0% from neonatologists, 9.3% paediatric neurologist. The median range for confidence was 4 (IQR3-5). Twenty-three interviews occurred. Thematic analysis revealed three themes: "Current culture on neonatal units", " Practicalities of the neurological examination in unwell neonates", and "Changing the culture". Most interviewees did not feel confident performing or interpreting the neurological examination in unwell neonates. Many units had a culture of seeing it as low priority, did not see its relevance in the acute management of unwell neonates. A few interviewees worked in units with a positive culture towards the neurological examination who used adapted standardised examinations and provided training. 72% of questionnaire responders wanted a new standardised neurological examination designed for the unwell neonate, which should be short, utilise pictures like the Hammersmith Neonatal Neurological Examination, contain an assessment of consciousness, be developmentally appropriate and achievable in unwell, ventilated neonates, be accompanied by a schematic to aid interpretation, and for greater training and assessments of competence., Conclusions: There are barriers preventing paediatricians being able to perform a neurological examination in unwell neonates, and a culture of neurophobia is common. A new standardised examination is needed, alongside aids to interpretation, training, and assessment., (© 2022. The Author(s).)

Intrathecal drug delivery is routinely used in the treatment and prophylaxis of varied central nervous system conditions, as doing so allows drugs to directly bypass the blood-brain barrier. However, the utility of this route of administration is limited by poor brain and spinal cord parenchymal drug uptake from the cerebrospinal fluid. We demonstrate that a simple noninvasive transcranial ultrasound protocol can significantly increase influx of cerebrospinal fluid into the perivascular spaces of the brain, to enhance the uptake of intrathecally administered drugs. Specifically, we administered small (~1 kDa) and large (~155 kDa) molecule agents into the cisterna magna of rats and then applied low, diagnostic-intensity focused ultrasound in a scanning protocol throughout the brain. Using real-time magnetic resonance imaging and ex vivo histologic analyses, we observed significantly increased uptake of small molecule agents into the brain parenchyma, and of both small and large molecule agents into the perivascular space from the cerebrospinal fluid. Notably, there was no evidence of brain parenchymal damage following this intervention. The low intensity and noninvasive approach of transcranial ultrasound in this protocol underscores the ready path to clinical translation of this technique. In this manner, this protocol can be used to directly bypass the blood-brain barrier for whole-brain delivery of a variety of agents. Additionally, this technique can potentially be used as a means to probe the causal role of the glymphatic system in the variety of disease and physiologic processes to which it has been correlated., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fetal ventriculomegaly is the the most common intracranial abnormality detected antenatally. When ventriculomegaly is mild and the only, isolated, abnormality detected (isolated mild ventriculomegaly (IMVM)) the prognosis is generally considered to be good. We aim to determine if there are features on in utero MRI (iuMRI) that can identify fetuses with IMVM who have lower risks of abnormal neurodevelopment outcome., Methods: We studied cases recruited into the MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero (MERIDIAN) study, specifically those with: confirmed IMVM, 3D volume imaging of the fetal brain and neurodevelopmental outcomes at 3 years. We explored the influence of sex of the fetus, laterality of the ventriculomegaly and intracranial compartmental volumes in relation to neurodevelopmental outcome., Findings: Forty-two fetuses met the criteria (33 male and 9 female). There was no obvious correlation between fetal sex and the risk of poor neurodevelopmental outcome. Unilateral IMVM was present in 23 fetuses and bilateral IMVM in 19 fetuses. All fetuses with unilateral IMVM had normal neurodevelopmental outcomes, while only 12/19 with bilateral IMVM had normal neurodevelopmental outcomes. There was no obvious correlation between measure of intracranial volumes and risk of abnormal developmental outcomes., Interpretation: The most important finding is the very high chance of a good neurodevelopmental outcome observed in fetuses with unilateral IMVM, which is a potentially important finding for antenatal counselling. There does not appear to be a link between the volume of the ventricular system or brain volume and the risk of poor neurodevelopmental outcome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Extracellular vesicles (EVs) are small, nanometre sized, membrane-enclosed structures released by cells and are thought to be crucial in cellular communication. The cargo of these vesicles includes lipids, proteins, RNAs and DNA, and control various biological processes in their target tissues depending on the parental and receiver cell's origin and phenotype. Recently data has accumulated in the role of EVs in embryo implantation and pregnancy, with EVs identified in the uterine cavity of women, sheep, cows, horses, and mice, in which they aid blastocyst and endometrial preparation for implantation. Herein is a critical review to decipher the role of extracellular vesicles in endometrial receptivity and their potential in reproductive therapies and diagnosis. The current knowledge of the function of embryo and endometrial derived EVs and their cargoes, with regards to their effect on implantation and receptivity are summarized and evaluated. The findings of the below review highlight that the combined knowledge on EVs deriving from the endometrium and embryo have the potential to be translated to various clinical applications including treatment, a diagnostic biomarker for diseases and a drug delivery tool to ultimately improve pregnancy rates., (Copyright © 2022. Published by Elsevier B.V.)

Background: Early developmental impairment (EDI) is common and has many aetiologies and, therefore, potential investigations. There are several published guidelines recommending aetiological investigations, and paediatricians' views of them varies. Little is known on the thought processes underlying clinical decisions in investigating EDI. This study aimed to describe the thought processes affecting clinical decisions on the investigation of EDI within a nationalised health care system., Methods: A qualitative descriptive study using semi-structured qualitative interviews performed in person or via video link with paediatricians who see children with EDI in England. As part of the interview, a case study of a fictional disease, Cavorite deficiency, modelled on biotinidase deficiency, was given to participants with the cost of testing, incidence and likelihood it would respond to treatment. This allowed exploration of cost without encumbrance from predisposing views and training on the condition. Thematic analysis was performed by iterative approach. Where participants stated they wanted to redirect money from investigations to treatment, were that even possible, we asked which services they would like to be better funded in their area., Results: Interviews were conducted with 14 consultant paediatricians: 9 Community / Neurodisability, 2 General paediatricians, and 3 Paediatric Neurologists. Two themes were identified: the value of an aetiological diagnosis to families and managing risk and probability when investigating EDI. The latter contained 4 subthemes: 'circumspection' involved blanket investigations chosen irrespective of phenotype and high regard for guidelines; 'accepting appropriate risk' involved participants choosing investigations based on clinical phenotype, recognising some aetiologies would be missed; consultants found they 'transitioned between practices' during their career; and 'improved practice' was thought possible with better evidence on how to stratify investigations based on phenotype. Services that were most frequently reported to need additional funding were therapy services, early community developmental services, management of behaviour, sleep and mental health, and educational support., Conclusions: There are many factors that influence paediatricians' choice of aetiological investigation in EDI, but clinical factors are the most important. Paediatricians want better evidence to allow them to select the right investigations for each child without a significant risk of missing an important diagnosis., (© 2022. The Author(s).)

Prospective parents whose fetus is diagnosed with a neurological anomaly go through a complex range of emotions. They describe their discussions of antenatal counselling from health care professionals as focusing too much on the nature of the anomaly involving unintelligible medical terminology, when what they really want is a picture of the best- and worst-case scenarios. Whilst information on the level of risk for their fetus is important, it is not the parents' primary concern. When statistics for risk are given, they may not be as well understood as the health care professionals think. This review discusses the published evidence on antenatal counselling and recommendations for explaining risk to parents of fetuses with neurological anomalies. From this data we make recommendations for the organization of antenatal counselling services., (© 2021 Mac Keith Press.)

After diagnosis of a fetal neurological anomaly, prospective parents want to know the best and worst-case scenarios and an estimation of the risk to their infant of having an atypical developmental outcome. The literature on developmental outcomes for fetal neurological anomalies is poor: studies are characterized by retrospective design, small sample size, often no standardized assessment of development, and differing definitions of anomalies. This review provides an aide-memoir on the risks of adverse neurodevelopmental outcome for ventriculomegaly, cortical anomalies, microcephaly, macrocephaly, agenesis of the corpus callosum, posterior fossa anomalies, and myelomeningocele, to assist healthcare professionals in counselling. The data in this review should be used alongside recommendations on counselling and service design described in part 1 to provide antenatal counselling., (© 2021 Mac Keith Press.)

Objective: Black youth experience racial discrimination at high rates. This study sought to further understand the longitudinal effects of racial discrimination on the mental health of Black youth by examining cross-lagged associations between perceived racial discrimination and depressive symptoms at the between-person (interindividual) level and the within-person (intraindividual) level., Method: A group of 346 Black youths (mean age 10.9 years) from the rural southern United States reported racial discrimination and depressive symptoms 4 times over 24.5 months. A cross-lagged panel model was used to examine between-person concurrent and lagged effects, and a random intercept cross-lagged panel model was used to examine within-person concurrent and lagged effects., Results: There were significant concurrent associations at all waves in both models. Additionally, there were significant lagged effects from perceived racial discrimination to depressive symptoms, but not from depressive symptoms to perceived racial discrimination, in both models., Conclusion: Youth experiencing higher levels of racial discrimination subsequently develop more depressive symptoms than youth experiencing less discrimination (between-person effects), and youth experiencing higher levels of discrimination relative to their own average subsequently report increases in depressive symptoms (within-person effects). These findings provide a rigorous test of conceptual models outlining the harmful effects of racial discrimination on mental health, add to a growing body of work documenting these effects on Black youth, and underscore the need for systemic changes to reduce the amount of discrimination Black youth experience and for interventions to promote resilience among Black youth in the face of cultural marginalization., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aim: To explore the attitudes of paediatric intensive care unit (PICU) health care professionals towards diagnosis and neurophysiological monitoring of seizures., Method: This study used an explanatory sequential mixed-methods approach, interconnecting quantitative and qualitative features, comprising questionnaires and interviews, with equal weighting between stages, of health care professionals working in UK PICUs. Interview data were analysed using thematic analysis and triangulated with questionnaire data., Results: Seventy-two questionnaires were returned: 49 out of 60 (71.0%) of respondents reported that seizures were extremely hard or somewhat hard to diagnose in a critically ill child, and 81.2% had seen misdiagnosis occur. Thematic analysis revealed two main themes: (1) feeling out of control when faced with 'grey areas'; and (2) regaining control, which compromised three subthemes: aggressive intervention, accurate diagnosis, and eschewing diagnosis., Interpretation: Health care professionals find accurate diagnosis of seizures difficult, particularly in sedated/paralysed children and those with chronic neurological disorders. They report they would like better educational opportunities on discriminating between epileptic and non-epileptic events to improve their confidence. Professionals want routine neurophysiological monitoring that can be applied and interpreted at the bedside throughout the day to regain a sense of control over their patient, direct treatment appropriately, and, potentially, improve outcomes, but report appropriate training and peer review are essential if it is to be introduced into routine care. What this study adds Paediatric intensive care unit (PICU) staff feel out of control when faced with diagnosing seizures. Neurophysiological monitoring is wanted to help diagnosis and treatment. Amplitude-integrated electroencephalography is the preferred, pragmatic tool by PICU staff., (© 2021 Mac Keith Press.)

Objective: Childhood maltreatment (CM) is a public health crisis that results in negative physical, mental health, and psychosocial (e.g., resource attainment) outcomes. Resource attainment is a critical outcome for marginalized populations, such as low-income African American women. This study addresses the gap in the literature regarding the association between CM and effectiveness of resource attainment and the potential mediating role of self-esteem in this association for African American women., Method: Data were gathered from a large public inner-city, university-affiliated health care system in the Southeastern United States. Participants selected were low-income African American women who have experienced intimate partner violence (IPV) and have attempted suicide in the prior year. The participants for this study completed the Childhood Trauma Questionnaire, the Beck Self-Esteem Scale, and the Effectiveness in Obtaining Resources Scale., Results: Mediation analyses using bootstrapping with 213 women revealed the powerful role self-esteem plays in explaining the link between CM and resource attainment in low-income African American women. Specifically, overall CM and four of its subtypes (emotional abuse, physical abuse, emotional neglect, and physical neglect) were all associated with decreased resource attainment via the effect of decreased self-esteem. Sexual abuse was the only subtype of CM not significantly associated with self-esteem nor effectiveness of resource attainment., Conclusion: This research highlights the importance of screening for CM, its subtypes, and resource attainment in this population and bolstering self-esteem through psychological interventions to increase women's capacity to effectively secure necessary community resources. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in the ability to perform activities of daily living. Ethnicity-related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among women for developing AD indicates that AA women with a parental history of AD are at great risk for developing AD. This phase I study assessed the impact of a 12 week, 20-lesson adapted Argentine Tango intervention ( n  = 24) to a no-contact control group ( n  = 10) on measures of plasma inflammatory markers, cognition, and motor and psychosocial performance in middle-aged AA woman at increased risk for AD by virtue of parental history. Some woman ( n  = 16) were also caregivers; thus, the impact of the intervention on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of cognition, including visuospatial and executive function, balance, and strength. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine, including reductions in IL-7 ( p   =  0.003), IFN-γ ( p   =  0.011), TNFα ( p   =  0.011), and MCP-1 ( p   =  0.042) compared to controls. Large effects were noted for the Tango group on tests of executive functioning ( d  = 0.89), and inhibition ( p   =  0.031). Participants in Tango improved in dynamic and static balance ( p   =  0.018) and functional lower body strength ( p   =  0.023). Secondary assessment revealed trends favoring the intervention group were noted in spatial cognition and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers. These data demonstrate substantial reductions in inflammatory biomarkers along with cognitive and motor improvements through a non-pharmacologic, affordable intervention among a small, well-characterized cohort of AA women with a parental history of AD., (Published by Elsevier B.V.)

The adverse impact of racial discrimination on youth, and particularly its impact on the development of depressive symptoms, has prompted attention regarding the potential for family processes to protect youth from these erosive effects. Evidence from non-experimental studies indicates that protective parenting behavior (PPB) which occurs naturally in many Black families can buffer youth from the negative impact of racial discrimination. Of interest is whether "constructed resilience" developed through family-centered prevention programming can add to this protective buffering. The current paper examines the impact of constructed resilience in the form of increased protective parenting using 295 families randomly assigned either to a control condition or to the Protecting Strong African American Families (ProSAAF) program, a family-based prevention program previously shown to enhance protective parenting. We found that baseline racial discrimination was predictive of change in youths' depressive symptoms across the pre-post study period. Second, we found that parents participating in ProSAAF, relative to those randomly assigned to the control group, significantly improved in their use of an intervention targeting PPB. Third, we found a significant effect of change in PPB on the association of discrimination with change in depressive symptoms. Finally, we found that ProSAAF participation buffered the impact of racial discrimination on change in depressive symptoms through change in PPB. Results provide experimental support for constructed resilience in the form of change in PPB and call for increased attention to the development of family-based intervention programs to protect Black youth from the pernicious effects of racial discrimination. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) for the treatment of abdominal pain in pancreatic cancer can be administered in three different ways, depending on the site of needle insertion: central injection (CI), bilateral injection (BI) and celiac ganglia neurolysis (CGN). This meta-analysis aimed to (1) estimate the overall efficacy of the EUS-CPN; (2) compare the efficacy of each of the three techniques; and (3) investigate demographic and disease characteristics as potential predictors of treatment response., Methods: We searched MEDLINE and EMBASE for studies that reported the proportion of treatment responders to EUS-CPN overall, and according to the technique used. We performed a random effects meta-analysis of proportions, and meta-regression was used to estimate the association between technique and clinical characteristics on treatment response. The safety profile was reviewed through narrative synthesis., Results: Overall response rate to EUS-CPN was 68% (95% CI 61%-74%) at week two and 53% (95% CI 45%-62%) at week four. There was no evidence of a significant difference in the response rates between the three techniques. Demographics and disease characteristics were not associated with treatment response. Serious complications have been reported for BI and CGN but not for CI. Moderate to high risk of bias was observed., Discussion: EUS-CPN is a useful adjunct to opioids in the management of pain. There is no evidence of a difference in the efficacy among the three techniques, however, CI is the only one for which serious complications have not been reported. Future research should focus on the appropriate timing of EUS-CPN (early versus on demand) and randomised comparison to establish the comparative efficacy of each technique., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Experiences of racial discrimination are common for Black Americans and have been associated with depression and sleep disturbance, factors likely involved in the insidious development of health disparities. The current study replicates these associations and examines longitudinal linkages., Method: Black American couples (men: N = 248, M age = 40, SD = 9; women: N = 277, M age = 37, SD = 7) and their children, aged 9 to 14 ( N = 276, M age = 11, SD = 1), completed measures of experiences of racial discrimination, depressive symptoms, and sleep problems at baseline and 8-month follow-up. In separate analyses for men, women, and youth, we examined concurrent and prospective associations of racial discrimination with depressive symptoms and sleep problems, then used longitudinal indirect effect models to examine whether depressive symptoms in response to racial discrimination led to increased sleep problems, or vice versa., Results: Racial discrimination was associated concurrently with depressive symptoms and sleep problems for all family members. Prospective associations were also found with depressive symptoms and sleep problems in fathers and youth, and sleep problems in mothers. Longitudinal models showed significant indirect effects of racial discrimination on change in sleep problems through depressive symptoms for fathers and mothers, and a similar, but nonsignificant, pattern in youth. There were no indirect effects on change in depressive symptoms through sleep problems., Conclusions: Persistent associations of racial discrimination with depressive symptoms and sleep problems reflect a lasting impact of racial discrimination. Because discrimination's effects on depression may contribute to increased sleep problems over time, interventions that buffer the effects of discrimination on depressive symptoms may also reduce sleep problems. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective: To compare participants with Parkinson disease (PD) motor subtypes, postural instability and gait difficulty (PIGD) (n=46) and tremor dominant (TD) (n=28), in cognitive and motor-cognitive assessments with the purpose of identifying associations between subtype and visuospatial, whole-body spatial, inhibition and/or switching, and planning and/or organizational aspects of cognitive and motor-cognitive function., Design: Retrospective cohort study. Fisher exact test was used for categorical variables, while 2-sample independent t tests were used to analyze continuous variables., Setting: Assessments took place at Emory University., Participants: Participants (N=72) were 40 years and older, had a clinical diagnosis of PD, exhibited 3 of the 4 cardinal signs of PD, had shown benefit from antiparkinsonian medications, and were in Hoehn and Yahr stages I-IV. Participants could walk 3 m or more with or without assistance., Interventions: Not applicable., Main Outcome Measures: Balance and mobility tests included Fullerton Advanced Balance Scale and the time needed to turn 360 degrees. Cognitive assessments included Montreal Cognitive Assessment, Brooks Spatial Memory Task, Color-Word Interference Test, Tower of London, Trail Making Test, Corsi Blocks, Serial 3s Subtraction, and Body Position Spatial Task. Motor-cognitive function measures included Four Square Step Test and Timed Up and Go., Results: Participants with PIGD performed lower than those with TD symptoms on mental status (P=.005), spatial memory (P=.027), executive function (P=.0001-.034), and visuospatial ability (P=.048)., Conclusions: Findings suggest that PIGD subtype is linked to greater deficits in spatial cognition, attentional flexibility and organizational planning, and whole-body spatial memory domains. These findings support the need for more personalized approaches to clinically managing PD., (Published by Elsevier Inc.)

Objective: To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC)., Design: We conducted a prospective cohort study of 83 147 participants (age range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI., Results: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (P trend =0.03) but not UC (P trend =0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all P interaction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD., Conclusion: In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD., Competing Interests: Competing interests: HK receives consulting fees from Abbvie. HK also receives grant support from Takeda and Pfizer. ATC receives consulting fees from Janssen, Pfizer and Bayer Pharma AG. SC has received consulting fees from Abbvie, Takeda and Ferring. OO has been Principal Investigaor (PI) on projects at Karolinska Institutet partly financed by investigator-initiated grants from Janssen, Ferring, Takeda and Pfizer. None of those studies have any relation to this study. Karolinska Institutet has received fees for OO's lectures and participation on advisory boards from Janssen, Ferring, Takeda and Pfizer regarding topics not related to this study. OO was supported by grants from the Swedish Medical Society (Project grants; Fund for Research in Gastroenterology; and Ihre Foundation), Mag-tarmfonden, Karolinska Institutet Foundations, Swedish Foundation for Strategic Research and Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet. JFL coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from Janssen., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1 -/- mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses., (Copyright © 2020 Marsh, Prestwich, Williams, Hart, Muir, Parker, Jonker, Heijink, Timens, Fife, Hussell, Hershenson, Bentley, Sun, Barksby, Borthwick, Stewart, Sabroe, Dockrell and Marriott.)